Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma-A Pilot Study.

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM.

Agricultural irrigation development in Castilla y León (Spain): driving forces and outcomes for landscape and sustainability in the 21st century.

Context: Agriculture relies on irrigation in many parts of the world, and the need for irrigation is increasing due to rising demands for agricultural products and climate change-induced alterations in rainfall patterns. However, irrigated agriculture has been found to damage ecosystems and threaten landscape sustainability.

Objectives: Against this background, there has been a recent development towards large-scale irrigation in Spain.

Endosomal membrane budding patterns in plants.

Multivesicular endosomes (MVEs) sequester membrane proteins destined for degradation within intralumenal vesicles (ILVs), a process mediated by the membrane-remodeling action of Endosomal Sorting Complex Required for Transport (ESCRT) proteins. In , endosomal membrane constriction and scission are uncoupled, resulting in the formation of extensive concatenated ILV networks and enhancing cargo sequestration efficiency. Here, we used a combination of electron tomography, computer simulations, and mathematical modeling to address the questions of when concatenated ILV networks evolved in plants and what drives their formation.

Social and ecological determinants of antimicrobial resistance in Africa: a systematic review of epidemiological evidence.

Background: Antimicrobial resistance (AMR) is one of the greatest global health problems for humans, animals, and the environment. Although the association between various factors and AMR is being increasingly researched, the need to understand the contribution of social and ecological determinants, especially in developing nations, remains. This review fills these knowledge gaps by synthesizing existing evidence on the social and ecological determinants of AMR in Africa.

Branched actin cortices reconstituted in vesicles sense membrane curvature.

The actin cortex is a complex cytoskeletal machinery that drives and responds to changes in cell shape. It must generate or adapt to plasma membrane curvature to facilitate diverse functions such as cell division, migration, and phagocytosis. Due to the complex molecular makeup of the actin cortex, it remains unclear whether actin networks are inherently able to sense and generate membrane curvature, or whether they rely on their diverse binding partners to accomplish this.

Clathrin coats partially preassemble and subsequently bend during endocytosis.

Eukaryotic cells use clathrin-mediated endocytosis to take up a large range of extracellular cargo. During endocytosis, a clathrin coat forms on the plasma membrane, but it remains controversial when and how it is remodeled into a spherical vesicle. Here, we use 3D superresolution microscopy to determine the precise geometry of the clathrin coat at large numbers of endocytic sites.

A systematic review and comparison of automated tools for quantification of fibrous networks.

Fibrous networks are essential structural components of biological and engineered materials. Accordingly, many approaches have been developed to quantify their structural properties, which define their material properties. However, a comprehensive overview and comparison of methods is lacking.

Membrane area gain and loss during cytokinesis.

In cytokinesis of animal cells, the cell is symmetrically divided into two. Since the cell's volume is conserved, the projected area has to increase to allow for the change of shape. Here we aim to predict how membrane gain and loss adapt during cytokinesis.

Tet Is Required for Maintaining Glial Homeostasis in Developing and Adult Fly Brains.

Ten-eleven translocation (TET) proteins are crucial epigenetic regulators highly conserved in multicellular organisms. TETs' enzymatic function in demethylating 5-methyl cytosine in DNA is required for proper development and TETs are frequently mutated in cancer. Recently, Tet (dTet) was shown to be highly expressed in developing fly brains and discovered to play an important role in brain and muscle development as well as fly behavior.

Auxin boosts energy generation pathways to fuel pollen maturation in barley.

Pollen grains become increasingly independent of the mother plant as they reach maturity through poorly understood developmental programs. We report that the hormone auxin is essential during barley pollen maturation to boost the expression of genes encoding almost every step of heterotrophic energy production pathways. Accordingly, auxin is necessary for the flux of sucrose and hexoses into glycolysis and to increase the levels of pyruvate and two tricarboxylic (TCA) cycle metabolites (citrate and succinate).

Histone H3.3 K27M and K36M mutations de-repress transposable elements through perturbation of antagonistic chromatin marks.

Histone H3.3 lysine-to-methionine substitutions K27M and K36M impair the deposition of opposing chromatin marks, H3K27me3/me2 and H3K36me3/me2. We show that these mutations induce hypotrophic and disorganized eyes in Drosophila eye primordia.

More than just a barrier: using physical models to couple membrane shape to cell function.

The correct execution of many cellular processes, such as division and motility, requires the cell to adopt a specific shape. Physically, these shapes are determined by the interplay of the plasma membrane and internal cellular driving factors. While the plasma membrane defines the boundary of the cell, processes inside the cell can result in the generation of forces that deform the membrane.

Competing pathways for the invagination of clathrin-coated membranes.

Clathrin-mediated endocytosis is the major pathway by which eukaryotic cells take up extracellular material, but it is still elusive which physical pathways are being taken during membrane invagination. From a continuum point of view, it can be driven by increases in coat stiffness, preferred curvature or line tension. Here we develop a comprehensive theoretical framework that can be solved analytically and that predicts the consequences of these different scenarios.

Ten-eleven translocation proteins and their role beyond DNA demethylation - what we can learn from the fly.

Ten-eleven Translocation (TET) proteins have emerged as a family of epigenetic regulators that are important during development and have been implicated in various types of cancers. TET is a highly conserved protein that has orthologues in almost all multicellular organisms. Here, we review recent literature on the novel substrate specificity of this family of DNA 5-methylcytosine demethylases on DNA 6-methyladenine and RNA 5-methylcytosine that were first identified in the invertebrate model .

Transcriptomic diversity in seedling roots of European flint maize in response to cold.

Background: Low temperatures decrease the capacity for biomass production and lead to growth retardation up to irreversible cellular damage in modern maize cultivars. European flint landraces are an untapped genetic resource for genes and alleles conferring cold tolerance which they acquired during their adaptation to the agroecological conditions in Europe.

Results: Based on a phenotyping experiment of 276 doubled haploid lines derived from the European flint landrace "Petkuser Ferdinand Rot" diverging for cold tolerance, we selected 21 of these lines for an RNA-seq experiment.

Forces during cellular uptake of viruses and nanoparticles at the ventral side.

Many intracellular pathogens, such as mammalian reovirus, mimic extracellular matrix motifs to specifically interact with the host membrane. Whether and how cell-matrix interactions influence virus particle uptake is unknown, as it is usually studied from the dorsal side. Here we show that the forces exerted at the ventral side of adherent cells during reovirus uptake exceed the binding strength of biotin-neutravidin anchoring viruses to a biofunctionalized substrate.

Dynamics of particle uptake at cell membranes.

Receptor-mediated endocytosis requires that the energy of adhesion overcomes the deformation energy of the plasma membrane. The resulting driving force is balanced by dissipative forces, leading to deterministic dynamical equations. While the shape of the free membrane does not play an important role for tensed and loose membranes, in the intermediate regime it leads to an important energy barrier.

QTL mapping and genome-wide prediction of heat tolerance in multiple connected populations of temperate maize.

Climate change will lead to increasing heat stress in the temperate regions of the world. The objectives of this study were the following: (I) to assess the phenotypic and genotypic diversity of traits related to heat tolerance of maize seedlings and dissect their genetic architecture by quantitative trait locus (QTL) mapping, (II) to compare the prediction ability of genome-wide prediction models using various numbers of KASP (Kompetitive Allele Specific PCR genotyping) single nucleotide polymorphisms (SNPs) and RAD (restriction site-associated DNA sequencing) SNPs, and (III) to examine the prediction ability of intra-, inter-, and mixed-pool calibrations. For the heat susceptibility index of five of the nine studied traits, we identified a total of six QTL, each explaining individually between 7 and 9% of the phenotypic variance.

Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness.

Our ability to manage acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption central to leukemogenesis, including improper histone methylation. Here we examine 16 histone H3 genes in 434 primary AML samples and identify Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), with higher incidence in secondary AML (9%).

Tet Is Expressed in Midline Glia and Is Required for Proper Axonal Development.

Ten-Eleven Translocation (TET) proteins are important epigenetic regulators that play a key role in development and are frequently deregulated in cancer. has a single homologous Tet gene () that is highly expressed in the central nervous system during development. Here, we examined the expression pattern of dTet in the third instar larval CNS and discovered its presence in a specific set of glia cells: midline glia (MG).

Stochastic Dynamics of Nanoparticle and Virus Uptake.

The cellular uptake of nanoparticles or viruses requires that the gain of adhesion energy overcomes the cost of plasma membrane bending. It is well known that this leads to a minimal particle size for uptake. Using a simple deterministic theory for this process, we first show that, for the same radius and volume, cylindrical particles should be taken up faster than spherical particles, both for normal and parallel orientations.

Targeting hormone refractory prostate cancer by in vivo selected DNA libraries in an orthotopic xenograft mouse model.

The targeting of specific tissue is a major challenge for the effective use of therapeutics and agents mediating this targeting are strongly demanded. We report here on an in vivo selection technology that enables the de novo identification of pegylated DNA aptamers pursuing tissue sites harbouring a hormone refractory prostate tumour. To this end, two libraries, one of which bearing an 11 kDa polyethylene glycol (PEG) modification, were used in an orthotopic xenograft prostate tumour mouse model for the selection process.

Volunteer and Career French Firefighters With High Cardiovascular Risk: Epidemiology and Exercise Tests.

Objective: We aim to identify cardiovascular risk factors in firefighters of Loire (French district) with a high cardiovascular risk and report results of a screening program using exercise tests.

Methods: A retrospective descriptive study was performed in a cohort of 158 career and 400 volunteer firefighters with a high cardiovascular risk who had undergone an exercise test.

Results: Five hundred fifty-eight exercise tests and cardiovascular profiles were analyzed.

Proteomics of Maize Root Development.

Maize forms a complex root system with structurally and functionally diverse root types that are formed at different developmental stages to extract water and mineral nutrients from soil. In recent years proteomics has been intensively applied to identify proteins involved in shaping the three-dimensional architecture and regulating the function of the maize root system. With the help of developmental mutants, proteomic changes during the initiation and emergence of shoot-borne, lateral and seminal roots have been examined.